Ensuring the security and privacy of RFID systems is paramount to prevent unauthorized access and data breaches. In addition, addressing the insecurity of public keys in RFID tags and preventing server-side tag distinction requires a multifaceted approach. This paper proposes an RFID-enabled protocol, calledRISE, Resource-Efficient RFID Security Protocol inIoT withS-Box andElliptic Curve Cryptography, that integrates S-box and elliptic curve cryptography (ECC) to enhance the security of RFID communication. The protocol leverages S-boxes to introduce non-linearity and confusion, thereby thwarting potential attacks such as cryptanalysis and replay attacks. Additionally, ECC is employed for key exchange and authentication, leveraging computational efficiency and strong security properties. Formal proofs and analysis results demonstrate thatRISEprovides robust security and can effectively resist various types of attacks.RISEpresents notable improvements, with an average 51.18% reduction in computational overhead compared to similar protocols. This advancement not only boosts performance but also enhances resource efficiency.